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BOR - Papers in Press, published online ahead of print July 12, 2006.
Biol Reprod 2006, 10.1095/biolreprod.106.051839
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BIOLOGY OF REPRODUCTION 75, 539–546 (2006)
DOI: 10.1095/biolreprod.106.051839
© 2006 by the Society for the Study of Reproduction, Inc.


Research Article

Neuroendocrine Changes in the Aging Reproductive Axis of Female Rhesus Macaques (Macaca mulatta)1

Jodi L. Downs 34 , and Henryk F. Urbanski 2 345  

Division of Neuroscience,3 Oregon National Primate Research Center, Beaverton, Oregon 97006 Departments of Physiology & Pharmacology4 Behavioral Neuroscience,5 Oregon Health & Science University, Portland, Oregon 97239

ABSTRACT

Femalerhesus macaques show monthly menstrual cycles and eventually enter menopause at approximately 25 yr of age. To help identify early biomarkers of menopause in this nonhuman primate, we monitored reproductive hormones longitudinally from aged female macaques during the transitions from premenopause to perimenopause and postmenopause and found that, indeed, elevated plasma FSH was a better predictive factor of menopause onset than age. In a second experiment, we compared reproductive hormone profiles of young adult macaques (8–10 yr old) with those of regularly cycling old macaques (approximately 24 yr old). Indwelling vascular catheters were used for remote blood collection for at least 100 consecutive days, thereby covering three complete menstrual cycles in each macaque. Plasma levels of estradiol, progesterone, LH, FSH, follicular phase inhibin B, and anti-müllerian hormone (AMH) were determined during each menstrual cycle and were averaged for each animal; group mean differences were analyzed using one-way ANOVA. Old premenopausal macaques showed regular menstrual cycles that were qualitatively indistinguishable from those of young macaques; peak plasma levels of estradiol, progesterone, and LH were not significantly different. In marked contrast, peak plasma FSH concentrations were significantly higher, while inhibin B and AMH levels were generally lower, in the old premenopausal macaques compared with those in the young macaques. These data provide further evidence that rhesus macaques serve as an excellent model to study underlying mechanisms of human menopause. Furthermore, the data suggest that an age-related change in FSH, inhibin B, and AMH secretion may be the first endocrine manifestation of the transition into perimenopause, potentially having value in predicting the onset of the perimenopausal transition.

aging, follicle-stimulating hormone, inhibin, menstrual cycle, neuroendocrinology


FOOTNOTES

1 Supported by grants AG-023477, AG-16935, AG-19100, AG-19914, HD-29186, and RR-00163 from the National Institutes of Health.

2 Correspondence: Henryk F. Urbanski, Division of Neuroscience, Oregon National Primate Research Center, 505 N.W. 185th Ave., Beaverton, OR 97006. FAX: 503 690 5384; urbanski{at}ohsu.edu




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